Replicating Human Organ Biology In Vitro

HemoShear’s Surrogate Vascular Systems Help Guide Drug Development

To understand biological and pharmacological responses in humans, HemoShear conducts experimental programs using human primary cells and creates systems that restore cells to an in vivo environment for healthy or disease conditions of interest. [Alexander Raths/Fotolia]

In 2005, a team of professors and researchers at the University of Virginia began a project to create a research tool that would replicate the biology of the human artery on the bench. Nicole Hastings, Ph.D., then a graduate student, along with Brett R. Blackman, Ph.D., and Brian R. Wamhoff, Ph.D., faculty members, designed a system that combined human primary endothelial cells and smooth muscle cells, which are the main cell types that comprise the human artery.

Most importantly, they exposed the endothelial cells to fluid movements that accurately mimic regional blood flow. This essential stimulus, along with other biophysical conditions, “turns on” the in vivo biology of the cells, thus creating a human surrogate vascular system.

The combination of multiple primary cell types, regional and complex hemodynamics, and biological transport were the core principles they developed in the laboratory and are now the foundational science of HemoShear. “Those were very exciting times for us,” says Dr. Hastings, who is now vp of operations.

HemoShear, founded in 2008, is now partnering with pharmaceutical, medical device, and other biotechnology companies to develop safer and more effective drugs using a unique scientific approach to in vitro based human relevant systems. In traditional drug development processes, early in vitro based experimentation using standard cell culture environments can create confounding data and results that are difficult to interpret. HemoShear says it can translate primary cell culture systems to the human biological condition, unveiling meaningful data for understanding drug-target interactions, mechanisms, and positive and negative output responses.

“HemoShear creates human-relevant systems to accurately replicate the biology of organ systems and diseases. We apply these methods to bridge the gap between traditional cell culture methods and human and animal pathobiology,” says Dr. Blackman, CSO.

Discovery Partnerships

Using its vascular system, HemoShear’s scientists are currently collaborating with pharmaceutical and biotechnology companies on R&D programs and foresee the opportunity to expand its methods into many other organs.

“When you expose vascular endothelial cells co-cultured with smooth muscle cells to very specific hemodynamic conditions, the cells can be reprogrammed to respond just as they do in the human body.

"We can make cells think they’re in the large arteries in the brain, or small vessels in the gut by applying region-specific hemodynamics,” says Dr. Wamhoff, vp of R&D.

“When studies are performed under these conditions, the results can better predict human responses and in turn, better inform scientific interpretation with our partners working on drug programs,” says Dr. Wamhoff.

Applying the same principles of cell co-cultures and hemodynamics, HemoShear has been developing an advanced liver system using human primary cells to assess liver toxicity, metabolism, and drug-drug interactions. The development work is being led by Ajit Dash, M.D., Ph.D. HemoShear believes that its human liver surrogate systems can guide companies in the discovery and selection of new drug candidates with better efficacy and safety profiles. “What is even more exciting is that we believe that we can create conditions to replicate liver diseases also,” says Dr. Wamhoff.

Human Response Database

In 2011, HemoShear was awarded a $4.3 million SBIR grant from the National Heart, Lung, and Blood Institute and has partnered with Expression Analysis, a Quintiles company, to develop the first comprehensive human response database for evaluating the vascular pharmacology of drug compounds.

Led by Robert Figler, Ph.D., HemoShear scientific director, the database will profile how human vascular cells respond at the genomic level to over 100 existing and novel drug compounds that span over 17 drug classes. Among the compounds being tested are drugs approved by the FDA, those withdrawn from the market, and some with black-box warnings.

Building upon this foundational Human Response Database, HemoShear will partner with its clients to determine risk profiles for their compounds as well as interrogate the database to exploit novel human biological effects across chemical and compound class for drug discovery and development initiatives.